JP4491460B2 - Filter for removing substances from blood products - Google Patents

Filter for removing substances from blood products Download PDF

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JP4491460B2
JP4491460B2 JP2006526611A JP2006526611A JP4491460B2 JP 4491460 B2 JP4491460 B2 JP 4491460B2 JP 2006526611 A JP2006526611 A JP 2006526611A JP 2006526611 A JP2006526611 A JP 2006526611A JP 4491460 B2 JP4491460 B2 JP 4491460B2
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filter
web
blood
polymer
particles
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JP2007505662A (en
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ジョルジョ・マリ
ステファノ・ヴェロネシ
ベルント・マテュー
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Fresenius Hemocare Italia SRL
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621—Extra-corporeal blood circuits
    • A61M1/3627—Degassing devices; Buffer reservoirs; Drip chambers; Blood filters
    • A61M1/3633—Blood component filters, e.g. leukocyte filters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3681—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation
    • A61M1/3683—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents
    • A61M1/3686—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by irradiation using photoactive agents by removing photoactive agents after irradiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • A61M2202/0439—White blood cells; Leucocytes

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  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • External Artificial Organs (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Filtering Materials (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Processing Of Meat And Fish (AREA)

Abstract

A filter device for the depletion of the leukocyte content from blood products comprising: a porous element comprising at least one fibrous web having a pore size suitable for leukocyte removal (possibly the range for the pore size should be defined), said web comprising fibres of a hydrophobic polymer coated with a hydrophilic polymer suitable to enhance the CWST of said hydrophobic polymer, characterised in that said web further includes adsorbent particles having a mean diameter lower than 30 mu m, said particles being bonded to said fibres by means of said hydrophilic polymer coating said fibres.

Description

発明の詳細な説明Detailed Description of the Invention

本発明は血液又は血液成分から白血球を除去するためのフィルターに関し、更に特定的には、たとえば全血を白血球枯渇血液成分に分離するために常用される血液バッグシステムのような血液精製装置における使用に適する白血球フィルターに関する。   The present invention relates to a filter for removing leukocytes from blood or blood components, and more particularly to use in a blood purification device such as a blood bag system commonly used to separate whole blood into leukocyte-depleted blood components. The present invention relates to a leukocyte filter suitable for use.

本発明が関連する血液フィルターには、典型的には、入口と出口を有するハウジングであって、さらに、そのハウジング内の出口と入口との間に挿入された、少なくとも１個の多孔性要素を含む。   A blood filter to which the present invention relates typically includes a housing having an inlet and an outlet, and further comprising at least one porous element inserted between the outlet and the inlet in the housing. Including.

多孔性要素は通常１層又はそれ以上のフィルター材料によって構成されていてもよいウェブ（ｗｅｂ）、典型的には不織生地からなる。   The porous element usually consists of a web, typically a nonwoven fabric, which may be constituted by one or more filter materials.

先行技術によれば、前記多孔性要素は、血液に適合性を持っているいかなる材料からも製造できるが、それは天然繊維又は合成繊維を含む繊維を形成していてもよい。   According to the prior art, the porous element can be manufactured from any material that is compatible with blood, but it may form fibers including natural fibers or synthetic fibers.

好適な材料は、たとえば特にポリオレフィン、ポリエステル及びポリアミドのような合成ポリマーである。   Suitable materials are, for example, synthetic polymers such as in particular polyolefins, polyesters and polyamides.

繊維性の白血球フィルターは先行技術にてよく知られており、たとえばＥＰ−Ａ−０３１３３４８号及びＥＰ−Ａ−０３９７４０３号に記載されている。   Fibrous leukocyte filters are well known in the prior art and are described, for example, in EP-A-0313348 and EP-A-0397403.

白血球フィルターで使用するために好適な材料は、溶融成型（melt-blowing）によって非常に細かな（好ましくは３μｍ以下の直径を持つ）繊維に加工するのに適する、合成樹脂である。   A suitable material for use in the leukocyte filter is a synthetic resin suitable for processing into very fine fibers (preferably having a diameter of 3 μm or less) by melt-blowing.

現在使用されている好適な材料は、ポリブチレンテレフタレート（ＰＢＴ）である。使用する繊維材料の表面特性は、材料の親水性の尺度である湿潤性又は限界湿潤表面張力（Critical Wetting Surface Tension: ＣＷＳＴ）が増大するように修正できる。   The preferred material currently used is polybutylene terephthalate (PBT). The surface properties of the fiber material used can be modified to increase the wettability or critical wetting surface tension (CWST), which is a measure of the hydrophilicity of the material.

この目的のためには、たとえばＰＢＴのような疎水性樹脂の繊維を、たとえば特に親水性のアクリル酸ポリマー又はコポリマー又は親水性ポリウレタンのような親水性が高いポリマーでコーティングする。   For this purpose, fibers of a hydrophobic resin such as PBT are coated with a highly hydrophilic polymer such as, for example, a particularly hydrophilic acrylic acid polymer or copolymer or hydrophilic polyurethane.

この繊維のために使用するポリマー材料は、ポリマー材料、特にＰＢＴに、ＥＰ−Ａ−０３１３３４８号に記載のようにして、たとえばヒドロキシル基と結合したアクリル酸基又はメチルアクリレート又はメチルメタアクリレート及びその組合せのように、エチレン的に不飽和な基を含む化合物、を表面グラフトすることによって親水性を高めることもできる。   The polymer material used for this fiber is a polymer material, in particular PBT, as described in EP-A-0313348, for example acrylic acid groups or methyl acrylate or methyl methacrylate combined with hydroxyl groups and combinations thereof. As described above, hydrophilicity can be enhanced by surface grafting a compound containing an ethylenically unsaturated group.

一般に、親水性の高いフィルターでは血小板の回収が増加することが米国特許第５５８０４６５号及び米国特許第４６１８５３３号に記載されている。   In general, it is described in US Pat. No. 5,580,465 and US Pat. No. 4,618,533 that platelet recovery is increased with highly hydrophilic filters.

当技術分野ではポリマー繊維とフィルター材料の全表面積を増大するための固体粒子とを含む複成白血球フィルターが公知である。   Compound leukocyte filters comprising polymer fibers and solid particles for increasing the total surface area of the filter material are known in the art.

米国特許第５４５４９４６号には、主としてガラス繊維及びマトリックスの空間内に配置された織物用繊維材料の微小繊維構造粒子からなる、連結したマトリックス繊維によって製造されたウェブを含む白血球を濾過するためのフィルター材料が記載されている。熱可塑性結合剤は、マトリックス繊維の交差部分に配置される。微小繊維構造粒子は、吸着性を持たず、その性質は多孔性ではない。   U.S. Pat. No. 5,454,946 discloses a filter for filtering leukocytes comprising webs made of connected matrix fibers, consisting mainly of glass fiber and fine fiber structured particles of textile fiber material disposed in the matrix space. The materials are listed. The thermoplastic binder is placed at the intersection of the matrix fibers. The fine fiber structure particles have no adsorptive property and are not porous.

米国特許第６３３７０２６号も、白血球枯渇化のための米国特許第５４５４９４６号に記載されているものと同じ型の濾過培地を記載しているが、ここではこの粒子は、表面積が小さくとも１００ｍ２／ｇと非常に大きく、また、マトリックス繊維に対する粒子の重量比は１００未満である。 US Pat. No. 6,337,026 also describes the same type of filtration media as described in US Pat. No. 5,454,946 for leukocyte depletion, where the particles have a surface area of at least 100 m 2 / g, and the weight ratio of particles to matrix fibers is less than 100.

米国特許第２００１／００−０９７５６Ａ１号は吸着剤粒子含有不活性マトリックスを含む生物学的組成物中にある低分子量化合物の濃度を低下させる装置を記載する。除去できる化合物であって、分子量１００ｇ／モル〜約３００００ｇ／モルを有するものには、たとえば光活性化産物のような病原不活化剤、アミノアクリジン、有機色素及びフェノチアジンが含まれる。このような装置が白血球枯渇化のために使用されるとの記載はない。   US 2001 / 00-09756A1 describes a device for reducing the concentration of low molecular weight compounds in a biological composition comprising an inert matrix containing adsorbent particles. Compounds that can be removed and have a molecular weight of 100 g / mole to about 30,000 g / mole include pathogen inactivators such as photoactivated products, aminoacridine, organic dyes and phenothiazines. There is no mention that such a device is used for leukocyte depletion.

本発明はフィルター材及びフィルター装置を提供し、これらは血液製剤及び全血又は血液成分から低分子量化合物を除くことができることに加えて、さらに白血球除去に高い効率を達成する。   The present invention provides filter media and filter devices, which, in addition to being able to remove low molecular weight compounds from blood products and whole blood or blood components, also achieve high efficiency in leukocyte removal.

本発明の主題は特許請求の範囲の欄に定義する。   The subject matter of the present invention is defined in the appended claims.

本発明の主題を構成するフィルター装置は、白血球の除去に適する孔径を持つ繊維性ウェブ少なくとも１種を含む多孔性要素を有する。このウェブには、疎水性ポリマーの臨界湿潤表面張力（ＣＷＳＴ）又は親水性を増大させる目的に適している親水性ポリマーで少なくとも部分的にはコーティングされた疎水性ポリマーの繊維が含まれる。適切な疎水性ポリマーには、ポリオレフィン、たとえばポリエチレン及びポリプロピレン、ポリアミド、ポリアラミド、ポリアクリル酸、ポリアクリロニトリル、酢酸セルロース、フッ化ポリビニリデン及びポリエステルが含まれる。好適なポリマーはポリブチレンテレフタレート（ＰＢＴ）である。   The filter device constituting the subject of the present invention has a porous element comprising at least one fibrous web having a pore size suitable for the removal of leukocytes. The web includes fibers of a hydrophobic polymer at least partially coated with a hydrophilic polymer suitable for the purpose of increasing the critical wetting surface tension (CWST) or hydrophilicity of the hydrophobic polymer. Suitable hydrophobic polymers include polyolefins such as polyethylene and polypropylene, polyamide, polyaramid, polyacrylic acid, polyacrylonitrile, cellulose acetate, polyvinylidene fluoride and polyester. A preferred polymer is polybutylene terephthalate (PBT).

不織ウェブの繊維直径は一般に０.０１μ〜５μの範囲内にある。   The fiber diameter of the nonwoven web is generally in the range of 0.01 μ to 5 μ.

不織無作為ウェブの繊維を製造するために好適な技術は溶融成形技術によるものである。この技術によって、繊維の本質的な多孔性と繊維直径分布とは、たとえば紡糸口金の特性及び設定、Ｄ.Ｃ.Ｄ.（Distance Conveyor to Die：ダイスへのディスタンスコンベヤー）、熱気及びポリマー量、工程温度、コレクターの吸引及び測位（たとえば傾斜）のような製造工程でのパラメータによって決定できる。   A suitable technique for producing the fibers of the nonwoven random web is by melt molding techniques. With this technique, the inherent porosity and fiber diameter distribution of the fiber can be determined, for example, by spinneret properties and settings, D.C.D. (Distance Conveyor to Die), hot air and polymer content, It can be determined by parameters in the manufacturing process such as process temperature, collector suction and positioning (eg tilt).

前記吸着剤粒子を、生物学的液体と接触する時に静的な又は流動的な条件のいずれかにおいて放出されないように繊維マトリックスに結合させる。本発明のフィルターに使用する吸着剤微粒子には、生体適合性材料で、又は少なくとも部分的に生体適合性材料でコーティングされた材料で製造した微粒子が含まれる。血液又は血漿から毒物を除去する目的に適合する吸着剤粒子又はビーズは、当技術分野で公知である。これらには、たとえばポリアクリル酸、ポリエステル、ポリアミド、ポリアクリルアミド及びポリスチレンコポリマーのようなポリマー材料が含まれるが；好適な材料はポリスチレン−ジビニルベンゼン（ＤＶＢ）又はポリアミドである。また、活性炭も使用できよう。粒子又はビーズの直径は一般に０.１〜２００ミクロンと広範囲に変化していてもよい。しかしながら、平均直径３０μｍ以下を持つ粒子を使用することが殊に好適である。また、本発明の範囲内にあることが意図されているものには、比表面積が２００ｍ２／ｇ〜約８００ｍ２／ｇ以上の内部微多孔性を持つ微粒子の使用がある。 The adsorbent particles are bonded to the fiber matrix so that they are not released in either static or fluid conditions when in contact with biological fluids. Adsorbent particulates used in the filter of the present invention include particulates made of a biocompatible material or a material at least partially coated with a biocompatible material. Adsorbent particles or beads suitable for the purpose of removing toxins from blood or plasma are known in the art. These include, for example, polymeric materials such as polyacrylic acid, polyesters, polyamides, polyacrylamides and polystyrene copolymers; suitable materials are polystyrene-divinylbenzene (DVB) or polyamides. Activated carbon could also be used. The diameter of the particles or beads may vary widely, generally from 0.1 to 200 microns. However, it is particularly preferred to use particles having an average diameter of 30 μm or less. Also, those that are intended to be within the scope of the invention is the use of fine particles having a specific surface area with 200 meters 2 / g to about 800 m 2 / g or more internal microporous.

疎水性繊維の親水性を強化するために使用する親水性ポリマーは、たとえばＶＡ／ＶＰ＝５０÷４のような様々なモル比で、酢酸ビニル（ＶＡ）とビニルピロリドン（ＶＰ）との重合によって得られるコポリマーから選択されるのが好ましい。   Hydrophilic polymers used to enhance the hydrophilicity of hydrophobic fibers can be obtained by polymerization of vinyl acetate (VA) and vinyl pyrrolidone (VP) at various molar ratios, for example VA / VP = 50/4. It is preferably selected from the resulting copolymers.

吸着剤粒子は当技術分野で公知の数種の方法、たとえば熱処理、包含法及びコーティングによって繊維表面に結合させてもよい。しかしながら、本発明によれば、好適な方法は、繊維材料の親水性を増強するために使用されるものと同じ親水性ポリマーを使用するコーティングによるものである。好適な方法によれば疎水性繊維（好ましくはＰＢＴ）の多孔性ウェブを、そのポリマー溶媒（たとえばアルコール性溶媒）及び該吸着剤粒子の懸濁液のための溶媒を含む、選択した親水性ポリマーの溶液を飽和するか又はそれに浸漬する。溶液内の親水性ポリマー濃度及び溶液内の粒子の量を適当に選択することによって、このように含浸ウェブを乾燥すれば、繊維表面に吸着剤粒子が結合し、また、繊維表面ならびに粒子表面が少なくとも部分的に親水性ポリマーでコーティングされたフィルター材料を獲得することが可能である。そのようなコーティングは吸着剤粒子の吸着特性を損なわないことが発見されている。好ましくはこの方法において、親水性ポリマーは前記の通り、好ましくはポリビニルピロリドンであるが、０.１〜５重量％の濃度の含浸溶液中で使用され、好ましくはポリスチレン−ＤＶＢ又はポリアミド製である吸着剤粒子は０.５〜１０重量％の量、好ましくは０.１〜１０重量％の量で溶液に加える。   The adsorbent particles may be bound to the fiber surface by several methods known in the art, such as heat treatment, inclusion methods and coatings. However, according to the present invention, the preferred method is by coating using the same hydrophilic polymer that is used to enhance the hydrophilicity of the fiber material. According to a preferred method, a selected hydrophilic polymer comprising a porous web of hydrophobic fibers (preferably PBT) comprising its polymer solvent (eg alcoholic solvent) and a solvent for the suspension of the adsorbent particles Saturate or soak the solution. By appropriately selecting the hydrophilic polymer concentration in the solution and the amount of particles in the solution, drying the impregnated web in this way causes the adsorbent particles to bind to the fiber surface, and the fiber surface and particle surface to It is possible to obtain a filter material that is at least partially coated with a hydrophilic polymer. It has been discovered that such coatings do not impair the adsorption properties of the adsorbent particles. Preferably in this process, the hydrophilic polymer is preferably polyvinylpyrrolidone as described above, but is used in an impregnation solution at a concentration of 0.1 to 5% by weight, preferably an adsorption made of polystyrene-DVB or polyamide. Agent particles are added to the solution in an amount of 0.5 to 10% by weight, preferably in an amount of 0.1 to 10% by weight.

典型的には、繊維ウェブに結合する吸着剤粒子の量は、ウェブ１ｇ当り０.０１〜０.５ｇ、好ましくはウェブ１ｇ当り０.１〜０.５ｇの範囲内にある。   Typically, the amount of adsorbent particles bound to the fibrous web is in the range of 0.01 to 0.5 g per gram of web, preferably 0.1 to 0.5 g per gram of web.

本発明のフィルター材料の総合的な多孔性は繊維の直径、微粒子の寸法、ならびに微粒子の分布及び濃度に基づく。次に、微粒子の使用によって、フィルターの白血球枯渇効率を増強するために（繊維材料の原特性（たとえば厚さ）を大幅に修正する必要なしに）、また、それ故に、その最終的プロファイルを最適化するために、材料の多孔性を低下させることが可能である。   The overall porosity of the filter material of the present invention is based on fiber diameter, particulate size, and particulate distribution and concentration. Secondly, the use of microparticles to enhance the leukocyte depletion efficiency of the filter (without the need to significantly modify the original properties (eg thickness) of the fiber material) and therefore optimize its final profile In order to reduce the porosity of the material.

表面積値の高い吸着剤粒子、及び特にポリスチレン−ＤＶＢ又はポリアミド粒子の使用によって、本発明のフィルター材料は、たとえば色素及び光活性分子、たとえば殺ウイルス強化剤、たとえばメチレンブルー、アクリジニル誘導体、ソラーレン及びソラーレン誘導体のような、低分子量物質の血液及び血液製剤からの除去も可能にする。   By the use of adsorbent particles with high surface area values, and in particular polystyrene-DVB or polyamide particles, the filter material according to the invention can be used, for example, for dyes and photoactive molecules such as virucidal enhancers such as methylene blue, acridinyl derivatives, psoralen and psoralen derivatives. It also allows removal of low molecular weight substances from blood and blood products.

実施例１：新材料製フィルターと常用材料製フィルターとの間の比較
新フィルター材料を用いた全血（ＷＢ）フィルターを、常用のフィルター材料で製造したフィルターと比較した。 Example 1: Comparison between a new material filter and a regular material filter A whole blood (WB) filter using a new filter material was compared to a filter made with a conventional filter material.

本発明のフィルター材料はポリビニルピロリドンでコーティングしたＰＢＴ繊維の不織ウェブで製造し、約１２μｍの平均直径及びウェブ１ｇ当り約０.４ｇの粒子含有量を持つ結合ポリアミド粒子を含んでいた。   The filter material of the present invention was made of a non-woven web of PBT fibers coated with polyvinylpyrrolidone and contained bound polyamide particles having an average diameter of about 12 μm and a particle content of about 0.4 g / g web.

各フィルターは、この新フィルター材料３０層で製造した。   Each filter was made with 30 layers of this new filter material.

常用フィルター材料は、新フィルター材料に使用したものと同じポリビニルピロリドン溶液でコーティングしたＰＢＴの不織ウェブであった。   The conventional filter material was a non-woven web of PBT coated with the same polyvinyl pyrrolidone solution used for the new filter material.

常用フィルター材料を用いたＷＢフィルターは、一つは４０層で作製し、他は３０層で作製した。   One WB filter using a common filter material was made of 40 layers, and the other was made of 30 layers.

全血（範囲４５０〜５５０ｍＬ）を無作為ドナーから採取して、ＣＰＤ７０ｍＬ入りのＰＶＣバッグに移した。提供された全血は全て１,４−ブタンジオールプレート下に２０〜２４℃に冷却した。濾過は重力によって行った。   Whole blood (range 450-550 mL) was taken from a random donor and transferred to a PVC bag with 70 mL CPD. All provided whole blood was cooled to 20-24 ° C. under 1,4-butanediol plates. Filtration was performed by gravity.

濾過した血液中の白血球（ＷＢＣ）は、Nageotteのヘモサイトメーターで計数した。   White blood cells (WBC) in the filtered blood were counted with a Nageotte hemocytometer.

得られた結果を次の表に要約する。

Figure 0004491460
The results obtained are summarized in the following table.
Figure 0004491460

これらの実験結果は、新フィルター材料が白血球枯渇について効率が高いこと、及び、常用フィルターより少量の材料で同じ結果を得ることができることを示す。   These experimental results indicate that the new filter material is more efficient for leukocyte depletion and that the same results can be obtained with less material than the conventional filter.

実施例２：ＲＣＣからのアクリジン誘導体の除去
ＰＳ−ＤＶＢマイクロスフェアをウェブ１ｇ当り０.４ｇの量で使用し、実施例１に記載した新フィルター材料でフィルターを製造した。 Example 2: Removal of acridine derivatives from RCC Filters were made with the new filter material described in Example 1 using PS-DVB microspheres in an amount of 0.4 g / g web.

マイクロスフェアの平均直径は３５ミクロンであり、表面積は９００ｍ２／ｇであった。この材料３０層を使用してフィルターを作製した。 The average diameter of the microspheres was 35 microns and the surface area was 900 m 2 / g. A filter was prepared using 30 layers of this material.

アクリジン誘導体をＳＡＧ−Ｍ（容積＝２７０ｍＬ）入りのＲＣＣのバッグに加えて、アクリジン誘導体濃度を２００マイクロモルとした。   The acridine derivative was added to an RCC bag containing SAG-M (volume = 270 mL) to adjust the acridine derivative concentration to 200 μmol.

濾過は重力によって行い、濾過後のアクリジン誘導体含有量は、１マイクロモル以下であった。   Filtration was performed by gravity, and the content of the acridine derivative after filtration was 1 micromolar or less.

常用のフィルター（４０層）では、アクリジン誘導体は除去されなかった。   A conventional filter (40 layers) did not remove the acridine derivative.

Claims (8)

−白血球除去に適する孔サイズを持つ繊維ウェブ少なくとも１種を含む多孔性要素；
−疎水性ポリマーのＣＷＳＴを増大させるために適する親水性ポリマーでコーティングされた疎水性ポリマーの繊維を含む該ウェブ；
を含む、血液製剤から白血球含有量の枯渇をさせるためのフィルター装置であって、
該ウェブが３０μｍ以下の平均直径を有する吸着剤粒子をさらに含み、その粒子が繊維をコーティングしている親水性ポリマーによって該繊維に結合していること、
該ウェブが、吸着剤粒子を０.１〜１０重量％で懸濁して含む親水性ポリマーの溶液に疎水性ポリマーの繊維ウェブを浸す（含浸する）ことによって得られること、
該ウェブが、繊維ウェブ材１ｇ当り０.０１〜０.５ｇの範囲の量で該粒子を含むこと、
および、該不織ウェブの繊維直径が、０．０１〜５μｍの範囲内であること
を特徴とする、フィルター装置。 - a porous element comprising a fiber 維U E blanking at least one having a pore size suitable for leukocyte removal;
The web comprising hydrophobic polymer fibers coated with a hydrophilic polymer suitable for increasing the CWST of the hydrophobic polymer;
A filter device for depleting leukocyte content from a blood product comprising :
The web further comprises adsorbent particles having an average diameter of 30 μm or less, the particles being bound to the fibers by a hydrophilic polymer coating the fibers;
The web is obtained by immersing (impregnating) a fibrous web of hydrophobic polymer in a solution of hydrophilic polymer comprising adsorbent particles suspended at 0.1 to 10% by weight ;
The web comprises the particles in an amount ranging from 0.01 to 0.5 g / g fiber web material;
And the fiber diameter of this nonwoven web exists in the range of 0.01-5 micrometers.
The filter device . 該親水性コーティングポリマーが、酢酸ビニルとビニルピロリドンとの重合によって得られるコポリマーから選択される、請求項１に記載のフィルター装置。  2. A filter device according to claim 1, wherein the hydrophilic coating polymer is selected from copolymers obtained by polymerization of vinyl acetate and vinyl pyrrolidone. 該吸着剤粒子がアクリル酸ポリマー、ポリエステル、ポリアミド、ポリアクリルアミド及びポリスチレン−ジビニルベンゼンから構成される群から選択される材料から製造される、請求項１または２に記載のフィルター装置。Adsorbent particles are acrylic polymers, polyesters, polyamides, poly acrylamide及 beauty polystyrene - is prepared from a material selected from the group consisting of divinylbenzene, filter device of claim 1 or 2. 該疎水性ポリマーがポリエチレン、ポリプロピレン、酢酸セルロース、ポリアミド、アクリル樹脂、ポリアクリロニトリル、フッ化ポリビニリデン、ポリアラミド及びポリエステルから構成される群から選択される、請求項１〜３のいずれか一項に記載のフィルター装置。Hydrophobic polymers of polyethylene, polypropylene, cellulose acetate, polyamide, acrylic resin, polyacrylonitrile, polyvinylidene fluoride, are selected from polyaramid and polyester Le that consists group, any one of claims 1 to 3 The filter device according to 1. 該疎水性ポリマーがポリブチレンテレフタレートであり、該吸着剤粒子がポリアミド又はポリスチレン−ジビニルベンゼンポリマーから作られ、さらに、該繊維を少なくとも部分的にコーティングするポリビニルピロリドンによって疎水性繊維に結合されている、請求項１〜４のいずれか一項に記載のフィルター装置。 The hydrophobic polymer is polybutylene terephthalate, the adsorbent particles are polyamide or polystyrene - made from divinylbenzene polymer, further coupled to a hydrophobic fiber by polyvinylpyrrolidone at least partially coating said fibers, The filter apparatus as described in any one of Claims 1-4 . 請求項１〜５のいずれか一項に記載のフィルターを通過させて血液製剤を供給することを含む、血液製剤から物質を除去する方法。A method for removing a substance from a blood product, the method comprising supplying the blood product through a filter according to any one of claims 1 to 5 . 請求項１〜５のいずれか一項に記載のフィルターを含む血液精製装置。The blood purification apparatus containing the filter as described in any one of Claims 1-5 . 請求項１〜５のいずれか一項に記載のフィルターを通過する第二のバッグに流通可能に連結した第一のバッグを含む、血液を白血球枯渇血液成分に分離するための血液バッグ装置からなる、請求項７に記載の血液精製装置。It comprises a blood bag device for separating blood into leukocyte-depleted blood components, including a first bag that is connected to the second bag that passes through the filter according to any one of claims 1-5. The blood purification apparatus according to claim 7 .
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